Method of making silicone containing contact lens with reduced amount of diluents

ABSTRACT

The present invention relates to a method of manufacturing a contact lens including the steps of: (i) adding reactive components to a mold, wherein the reactive components comprise (a) at least one hydroxy-containing silicone component having a weight average molecular weight from about 200 to about 15,000 g/mole and (b) at least one mono-ether terminated, mono-methacrylate terminated polyethylene glycol having a weight average molecular weight from about 200 to about 10,000 g/mole; (ii) curing the reactive components within the mold to form the contact lens; and (iii) removing the contact lens from said mold.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/663,719, filed on Jun. 25, 2012 entitled METHOD OF MAKINGSILICONE CONTAINING CONTACT LENS WITH REDUCED AMOUNT OF DILUENTS, thecontents of which are incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to the method of making siliconecontaining contact lens.

BACKGROUND OF THE INVENTION

Contact lenses have been used commercially to improve vision since the1950s. The first contact lenses were made of hard materials. Althoughthese lenses are still currently used, they are not suitable for allpatients due to their poor initial comfort and their relatively lowpermeability to oxygen. Later developments in the field gave rise tosoft contact lenses, based upon hydrogels, which are extremely populartoday. Many users find soft lenses are more comfortable, and increasedcomfort levels can allow soft contact lens users to wear their lenseslonger than users of hard contact lenses.

It is desirable to manufacture silicone-containing contact lens usingreduced or no diluent systems, which can enable the cured polymer to be“dry released” from the mold parts, placed directly into the finalpackage containing packing solution for equilibration. Typically, thezero diluent systems containing high levels of PVP tend to produce curedlenses that are very brittle. These lenses when released usingmechanical force are susceptible to physical damage. Applicants havefound the incorporation of at least one mono-ether terminated,mono-methacrylate terminated polyethylene glycol significantly lowersthe level of brittleness in the cured lenses. Thus, the cured lenses areless liable to fracture when subjected to stress during the lens releaseprocess. The at least one mono-ether terminated, mono-methacrylateterminated polyethylene glycol also allows for tuning the visco-elasticproperties of the cured polymers for desirable mechanical lens releasewithout the use of liquids.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a method ofmanufacturing a contact lens, said method comprising the steps of:

(i) adding reactive components to form a reactive mixture, wherein saidreactive components comprise (a) at least one hydroxy-containingsilicone component having a weight average molecular weight from about200 to about 15,000 g/mole and (b) at least one monofunctionalpolyethylene glycol having a weight average molecular weight from about200 to about 10,000 g/mole; and less than about 15 wt % diluents;

(ii) curing said reactive components within said mold to form saidcontact lens comprising a polymer having a Tg (heating) of less thanabout 125 C; and

(iii) dry removing said contact lens from said mold.

In another aspect, the present invention feature a contact lensmanufactured according to the above method.

Other features and advantages of the present invention will be apparentfrom the detailed description of the invention and from the claims.

DETAILED DESCRIPTION OF THE INVENTION

It is believed that one skilled in the art can, based upon thedescription herein, utilize the present invention to its fullest extent.The following specific embodiments can be construed as merelyillustrative, and not limitative of the remainder of the disclosure inany way whatsoever.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention belongs. Also, all publications, patentapplications, patents, and other references mentioned herein areincorporated by reference.

DEFINITIONS

As used herein “reactive mixture” refers to the mixture of components(both reactive and non-reactive) which are mixed together and subjectedto polymerization conditions to form the silicone hydrogels and contactlenses of the present invention. The reactive mixture comprises reactivecomponents such as monomers, macromers, prepolymers, cross-linkers, andinitiators, and additives such as wetting agents, release agents, dyes,pigments, light absorbing compounds such as UV absorbers andphotochromic compounds, any of which may be reactive or non-reactive butare capable of being retained within the resulting lens, as well aspharmaceutical and neutriceutical compounds, and any diluents. It willbe appreciated that a wide range of additives may be added based uponthe lens which is made, and its intended use.

Concentrations of components of the reactive mixture are given in weight% of all components in the reaction mixture, excluding any diluents.When diluents are used their concentrations are given as weight % basedupon the amount of all components in the reaction mixture and thediluents.

As used herein “reactive groups” are groups that can undergo freeradical and/or tionic polymerization.

As used herein, “polymerizable” means that the compound comprises atleast one polymerizable functional group, such as acrylate,methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinylamide,and styryl functional groups. “Non-polymerizable” means that thecompound does not comprise such a polymerizable functional group.

As used herein, “hydrophobic” means that the compound(s)/monomer(s) isinsoluble in a mixture of 10 weight parts in 90 weight parts of water,and “hydrophilic” means that the compound(s)/monomer(s) is soluble in amixture of 10 parts in 90 weight parts of water. The solubility of asubstance is evaluated at 20° C.

As used herein, the term “alkyl” refers to a hydrocarbon group of from 1to 20 carbons, unless otherwise indicated.

Silicone Component

The reactive mixture contains at least one silicone-containing componentcomprising at least one hydroxy group (“hydroxy-containing siliconecomponent”) and having a weight average molecular weight from about 200to about 15,000 g/mole, such as from about 300 to about 2,000 g/mole. Asilicone-containing component (or silicone component) is one thatcontains at least one [—Si—O—Si] group, in a monomer, macromer orprepolymer. In one embodiment, the Si and attached 0 are present in thesilicone-containing component in an amount greater than 20 weightpercent, such as greater than 30 weight percent of the total molecularweight of the silicone-containing component. Useful hydroxy-containingsilicone components include polymerizable functional groups such asacrylate, methacrylate, acrylamide, methacrylamide, N-vinyl lactam,N-vinylamide, and styryl functional groups. Examples ofhydroxy-containing silicone components which are useful in thisinvention may be found in U.S. Pat. Nos. 4,139,513; 4,139,692;5,998,498; and 5,070,215.

Suitable hydroxyl-containing silicone components include compounds ofFormula I

wherein:

R¹ is independently selected from reactive groups, alkyl groups, or arylgroups, any of the foregoing which may further comprise functionalityselected from hydroxy, amino, oxa, carboxy, alkyl carboxy, alkoxy,amido, carbamate, carbonate, halogen or combinations thereof; andsiloxane chains comprising 1-100 Si—O repeat units which may furthercomprise functionality selected from alkyl, hydroxy, amino, oxa,carboxy, alkyl carboxy, alkoxy, amido, carbamate, halogen orcombinations thereof;

where b=0 to 500 (such as 0 to 100, such as 0 to 20), where it isunderstood that when b is other than 0, b is a distribution having amode equal to a stated value; and

wherein at least one R¹ comprises a reactive group, and in someembodiments from one to three R¹ comprise reactive groups and at leastone R group comprises one or more hydroxyl group.

Non-limiting examples of radical reactive groups include(meth)acrylates, styryls, vinyls, vinyl ethers,C₁₋₆alkyl(meth)acrylates, (meth)acrylamides, C₁₋₆alkyl(meth)acrylamides,N-vinyllactams, N-vinylamides, C₂₋₁₂alkenyls, C₂₋₁₂alkenylphenyls,C₂₋₁₂alkenylnaphthyls, C₂₋₆alkenylphenylC₁₋₆alkyls, O-vinylcarbamatesand O-vinylcarbonates. Non-limiting examples of cationic reactive groupsinclude vinyl ethers or epoxide groups and mixtures thereof. In oneembodiment the free radical reactive groups comprises (meth)acrylate,acryloxy, (meth)acrylamide, and mixtures thereof.

In one embodiment b is zero, one R¹ is a reactive group, and at least 3R¹ are selected from monovalent alkyl groups having one to 16 carbonatoms, and in another embodiment from monovalent alkyl groups having oneto 6 carbon atoms, in another embodiment one R¹ is a reactive group, twoR¹ are trialkyl siloxanyl group and the remaining R¹ are methyl, ethylor phenyl and in a further embodiment one R¹ is a reactive group, two R¹are trialkyl siloxanyl groups and the remaining R¹ are methyl.Non-limiting examples of silicone components of this embodiment includepropenoicacid,-2-methyl-,2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]propylester (“SiGMA”; structure in Formula II),

and 2-hydroxy-3-methacryloxypropyloxypropyl-tris(trimethylsiloxy)silane.

In another embodiment, b is 2 to 20, 3 to 20, 3-16, 3 to 15 or in someembodiments 3 to 10; at least one terminal R¹ comprises a reactive groupand the remaining R¹ are selected from monovalent alkyl groups having 1to 16 carbon atoms, and in another embodiment from monovalent alkylgroups having 1 to 6 carbon atoms. In yet another embodiment, b is 3 to15, one terminal R¹ comprises a reactive group, the other terminal R¹comprises a monovalent alkyl group having 1 to 6 carbon atoms and theremaining R¹ comprise monovalent alkyl group having 1 to 3 carbon atoms.Non-limiting examples of silicone components of this embodiment include(mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminatedpolydimethylsiloxane (400-2000, or 400-1600 MO (“OH-mPDMS”; structure inFormula III).

In one embodiment a mixture of hydroxyl-containing silicone componentsmay be used to improve the compatibility of the reactive mixture.

In another embodiment, the hydroxyl-containing silicone componentcomprises a polydimethylsiloxane bis-methacrylate with pendent hydroxylgroups, such as compound C2, C4 or R2 described in US Patent ApplicationNo. 2004/0192872 or such as is described in Examples XXV, XXVIII, orXXXii in U.S. Pat. No. 4,259,467, polymerizable polysiloxanes withpendant hydrophilic groups such as those disclosed in U.S. Pat. No.6,867,245. In some embodiments the pendant hydrophilic groups arehydroxyalkyl groups and polyalkylene ether groups or combinationsthereof. The polymerizable polysiloxanes may also comprise fluorocarbongroups. An example is shown as structure B3.

Other silicone components suitable for use in this invention includethose described as “C” Materials in WO 96/31792. Another class ofsuitable silicone-containing components includes silicone containingmacromers made via GTP, such as the hydroxyl-containing macromersdisclosed in U.S. Pat. Nos. 5,314,960, 5,371,147 and 6,367,929.

In one embodiment of the present invention where a modulus of less thanabout 120 psi is desired, the majority of the mass fraction of thesilicone-containing components used in the lens formulation shouldcontain only one polymerizable functional group (“monofunctionalsilicone containing component”). In this embodiment, to insure thedesired balance of oxygen transmissibility and modulus it is preferredthat all components having more than one polymerizable functional group(“multifunctional components”) make up no more than 10 mmol/100 g of thereactive components, and preferably no more than 7 mmol/100 g of thereactive components.

In one embodiment, the silicone component is selected from the groupconsisting of bis-3-acryloxy-2-hydroxypropyloxypropylpolydialkylsiloxane; mono-(3-methacryloxy-2-hydroxypropyloxy)propylterminated, mono-alkyl terminated polydialkylsiloxane; and mixturesthereof. In one embodiment, the silicone component is selected frombis-3-acryloxy-2-hydroxypropyloxypropyl polydialkylsiloxane; andmono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated, mono-butylterminated polydialkylsiloxane; and mixtures thereof.

Examples of other silicone components include the following:

In one embodiment, the silicone component has an average molecularweight of from about 400 to about 4000 daltons.

The silicone containing component(s) may be present in amounts fromabout 10 to about 87 weight %, and in some embodiments from about 10 andabout 80 and in other embodiments from about 20 and about 70 weight %,based upon all reactive components of the reactive mixture (e.g.,excluding diluents).

Monofunctional Terminated Polyethylene Glycol

The reactive mixture also contains at least one monofunctionalpolyethylene glycol having a weight average molecular weight from about200 to about 10,000 g/mole, such as from about 200 to about 2,000g/mole. The monofunctional polyethylene glycol comprises only onepolymerizable group and may be a mono-ether terminated,mono-(meth)acrylate or (meth)acrylamide terminated polyethylene glycol.Examples of mono-ether terminal groups include, but are not limited to,C1-C6 alkoxy groups, such as methoxy and ethoxy or alkoxy groupscomprising up to 8 carbons. Examples of such mono-ether terminated,mono-methacrylate terminated polyethylene glycol include, but are notlimited to, mPEG 475 (polyethyleneglycol (475 Mw) monomethylethermonomethacrylate, available from Sigma-Aldrich, St. Louis, Mo. USA(“mPEG475”). The monofunctional polyethylene glycol(s) may be present inamounts from about 3 and about 30 weight %, from about 5 to about 30weight %, and in other embodiments from about 10 and about 30 weight %,based upon all reactive components of the reactive mixture (e.g.,excluding diluents if any).

The monofunctional polyethylene glycol(s) provide the resulting cured,prehydrated polymers with glass transition temperature upon heating, Tg,of less than about 125 C, or between about 115 and about 125 C. Thisprovides desirable dry release characteristics, and particularly aresistance to fracturing. The properties of the hydrated lens aresubstantially unchanged from reactive mixtures which do not comprise atleast one monofunctional polyethylene glycol.

Other Hydrophilic Components

In one embodiment, the reactive mixture/lens may also include at leastone other hydrophilic component. In one embodiment, these hydrophiliccomponents can be any of the hydrophilic monomers known to be useful tomake hydrogels.

One class of suitable hydrophilic monomers includes acrylic- orvinyl-containing monomers. Such hydrophilic monomers may themselves beused as crosslinking agents, however, where hydrophilic monomers havingmore than one polymerizable functional group are used, theirconcentration should be limited as discussed above to provide a contactlens having the desired modulus.

The term “vinyl-type” or “vinyl-containing” monomers refer to monomerscontaining the vinyl grouping (Y—CH═CH₂) and that are capable ofpolymerizing, where Y is not a carbonyl (C═O) group.

Hydrophilic vinyl-containing monomers which may be incorporated into thereactive mixtures/hydrogels/lenses of the present invention include, butare not limited to, monomers such as N-vinyl amides, N-vinyl lactams(e.g. N-vinylpyrrolidone or NVP), N-vinyl-N-methyl acetamide,N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide,with NVP being preferred.

“Acrylic-type” or “acrylic-containing” monomers are those monomerscontaining the acrylic group: (CH₂=CRCOX) wherein R is H or CH₃, and Xis O or N, which are also known to polymerize readily, such asN,N-dimethyl acrylamide (DMA), acrylamide, 2-hydroxyethyl methacrylate(HEMA), glycerol methacrylate, 2-hydroxyethyl methacrylamide,polyethyleneglycol monomethacrylate, methacrylic acid, mixtures thereofand the like.

Other hydrophilic monomers that can be employed in the inventioninclude, but are not limited to, polyoxyethylene alcohols having one ormore of the terminal hydroxyl groups replaced with a functional groupcontaining a polymerizable double bond. Examples include polyethyleneglycol, ethoxylated alkyl glucoside, and ethoxylated bisphenol A reactedwith one or more molar equivalents of an end-capping group such asisocyanatoethyl methacrylate (“IEM”), methacrylic anhydride,methacryloyl chloride, vinylbenzoyl chloride, or the like, to produce apolyethylene polyol having one or more terminal polymerizable olefinicgroups bonded to the polyethylene alcohol through linking moieties suchas carbamate or ester groups.

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215 and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

In one embodiment the other hydrophilic component comprises at least onehydrophilic monomer such as DMA, HEMA, glycerol methacrylate,2-hydroxyethyl methacrylamide, NVP, N-vinyl-N-methyl acrylamide,polyethyleneglycol monomethacrylate, and combinations thereof. Inanother embodiment, the other hydrophilic monomers comprise at least oneof DMA, HEMA, NVP and N-vinyl-N-methyl acrylamide and mixtures thereof.In another embodiment, the other hydrophilic monomer comprises DMAand/or HEMA.

The other hydrophilic component(s) (e.g., DMA or HEMA) may be present ina wide range of amounts, depending upon the specific balance ofproperties desired. In one embodiment, the amount of the hydrophiliccomponent is up to about 60 weight %, such as from about 5 and about 40weight %, from about 10 to about 40 weight %, from about 13 to about 40weight %, or from about 13 to about 30 weight %, based upon the weightof the reactive components. In one embodiment, the weight ratio of (i)said hydrophilic components (e.g., DMA or HEMA) and (ii) said at leastone at least one mono-methacrylate terminated polyethylene glycol isfrom about 25:75 to about 75:25.

In another embodiment the amount of (meth)acrylamide monomers is lessthan about 10 weight % or between about 3 and about 10 weight % of allcomponents in the reaction mixture, excluding any diluents. Examples of(meth)acrylamide monomers include, DMA, acrylamide, N-vinyl-N-methylacrylamide, N-vinylacrylamide, mixtures thereof and the like.

The amount of hydroxyl alkyl monomers, may be between about 10 and about20 weight % of all components in the reaction mixture, excluding anydiluents. Examples of hydroxyl alkyl monomers include HEMA,2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylamide, 2-hydroxypropylmethacrylamide, 2-hydroxypropyl methacrylate, 2-hydroxybutylmethacrylamide, 2-hydroxybutyl methacrylate, mixtures thereof and thelike,

Polymerization Initiator

One or more polymerization initiators may be included in the reactionmixture. Examples of polymerization initiators include, but are notlimited to, compounds such as lauryl peroxide, benzoyl peroxide,isopropyl percarbonate, azobisisobutyronitrile, and the like, thatgenerate free radicals at moderately elevated temperatures, andphotoinitiator systems such as aromatic alpha-hydroxy ketones,alkoxyoxybenzoins, acetophenones, acylphosphine oxides, bisacylphosphineoxides, and a tertiary amine plus a diketone, mixtures thereof and thelike. Illustrative examples of photoinitiators are 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one,bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide(DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenyl phosphineoxide (IRGACURE®819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide and2,4,6-trimethylbenzoyl diphenylphosphine oxide, benzoin methyl ester anda combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.Commercially available visible light initiator systems include, but arenot limited to, IRGACURE® 819, IRGACURE®1700, IRGACURE®1800,IRGACURE®1850 (all from Ciba Specialty Chemicals) and Lucirin TPOinitiator (available from BASF). Commercially available UVphotoinitiators include Darocur 1173 and Darocur 2959 (Ciba SpecialtyChemicals). These and other photoinitators which may be used aredisclosed in Volume III, Photoinitiators for Free Radical Cationic &Anionic Photopolymerization, 2^(nd) Edition by J. V. Crivello& K.Dietliker; edited by G. Bradley; John Wiley and Sons; New York; 1998.

The polymerization initiator is used in the reaction mixture ineffective amounts to initiate photopolymerization of the reactionmixture, such as from about 0.1 to about 2 weight %. Polymerization ofthe reaction mixture can be initiated using the appropriate choice ofheat or visible or ultraviolet light or other means depending on thepolymerization initiator used. Alternatively, initiation can beconducted without a photoinitiator using, for example, e-beam. However,when a photoinitiator is used, the preferred initiators arebisacylphosphine oxides, such as bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (IRGACURE® 819) or a combination of 1-hydroxycyclohexylphenyl ketone and DMBAPO, and in another embodiment the method ofpolymerization initiation is via visible light activation.

Internal Wetting Agent

In one embodiment, the reaction mixture includes one or more internalwetting agents. Internal wetting agents may include, but are not limitedto, high molecular weight, hydrophilic polymers such as those describedin U.S. Pat. Nos. 6,367,929; 6,822,016; 7,786,185; PCT PatentApplication Nos. WO03/22321 and WO03/22322, or reactive, hydrophilicpolymers such as those described in U.S. Pat. No. 7,249,848. Examples ofinternal wetting agents include, but are not limited to, polyamides suchas poly(N-vinyl pyrrolidone), poly(dimethyl acrylamide) and poly(N-vinyl-N-methyl acetamide), polyN-vinyl acetamide, polyacrylamide andcopolymers thereof. Suitable comonomers include acrylic acid,methacrylic acid, 2-hydroxyethyl methacrylate, reactive polyethyleneglycol monomers, combinations thereof and the like.

The internal wetting agent(s) may be present in a wide range of amounts,depending upon the specific parameter desired. In one embodiment, theamount of the wetting agent(s) is up to about 50 weight %, up to about30 weight %, such as from about 5 and about 40 weight %, from about 5and about 30 weight %, such as from about 6 to about 40 weight % or fromabout 6 to about 25 weight % based upon all % of all components in thereaction mixture, excluding any diluents.

Other Components

Other components that can be present in the reaction mixture used toform the contact lenses of this invention include, but are not limitedto, ultra-violet absorbing compounds, medicinal agents, antimicrobialcompounds, copolymerizable and nonpolymerizable dyes, copolymerizableand non-copolymerizable photochromic compounds, ionic monomers orcomponents, surfactants, release agents, reactive tints, pigments,combinations thereof and the like. In one embodiment, the sum ofadditional components may be up to about 20 wt %.

Diluents

In one embodiment, the reactive components (e.g., silicone-containingcomponents, hydrophilic monomers, wetting agents, and/or othercomponents) are mixed together either with or without a diluent to formthe reaction mixture. In one embodiment, the reactive mixture comprisesless than about twenty percent (e.g., such as less than about tenpercent, less than about five percent, or less than about one percent)by weight, of one or more diluents, or comprises no diluents.

In one embodiment where a diluent is used, the diluent has a polaritysufficiently low to solubilize the non-polar components in the reactivemixture at reaction conditions. One way to characterize the polarity ofthe diluents of the present invention is via the Hansen solubilityparameter, op. In certain embodiments, the Op is less than about 10, andpreferably less than about 6. Suitable diluents are further disclosed inUS Patent Application No. 20100280146 and U.S. Pat. No. 6,020,445.

In another embodiment the selected diluents are ophthalmicallycompatible, at least in small concentrations. Thus, in one embodimentthe diluent is ophthalmically compatible in concentrations of up to 5weight % in the packing solution and in some embodiments, up to 1% byweight of the packing solution.

Classes of suitable diluents include, without limitation, alcoholshaving 2 to 20 carbons, amides having 10 to 20 carbon atoms derived fromprimary amines, ethers, polyethers, ketones having 3 to 10 carbon atoms,and carboxylic acids having 8 to 20 carbon atoms. As the number ofcarbons increase, the number of polar moieties may also be increased toprovide the desired level of water miscibility. In some embodiments,primary and tertiary alcohols are preferred. Preferred classes includealcohols having 4 to 20 carbons and carboxylic acids having 10 to 20carbon atoms.

In one embodiment, the diluents are selected from 1,2-octanediol, t-amylalcohol, 3-methyl-3-pentanol, decanoic acid, 3,7-dimethyl-3-octanol,tripropylene glycol methyl ether (TPME), 1, 2-propanediol, glycerol,polyethylene glycol having molecular weights between about 200 and about30,000, methyl glucose ethers, such as Glucam polymers, butoxyethylacetate, mixtures thereof and the like.

In one embodiment, the diluents are selected from diluents that havesome degree of solubility in water. In some embodiments at least aboutthree percent of the diluent is miscible water. Examples of watersoluble diluents include, but are not limited to, 1-octanol, 1-pentanol,1-hexanol, 2-hexanol, 2-octanol, 3-methyl-3-pentanol, 2-pentanol, t-amylalcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol,2-ethyl-1-butanol, ethanol, 3,3-dimethyl-2-butanol, decanoic acid,octanoic acid, dodecanoic acid, 1-ethoxy-2-propanol,1-tert-butoxy-2-propanol, EH-5 (commercially available from EthoxChemicals), 2,3,6,7-tetrahydroxy-2,3,6,7-tetramethyl octane,9-(1-methylethyl)-2,5,8,10,13,16-hexaoxaheptadecane,3,5,7,9,11,13-hexamethoxy-1-tetradecanol, mixtures thereof and the like.

Suitable ranges for the components of the present invention are shown inthe Table below.

Component Concentration (wt %) Silicone component 10-87, 10-80, 20-70PEG 3-30 Hydrophilic component 5-40, 10-40, 13-40, 13-30 Wetting agent0-50; 5-40, 6-40, 10-20 Other 0-20 Diluent ≦20, <15, ≦10, ≦5, ≦1, 0

It will be appreciated that the amount of the components in eachembodiment will add up to 100. Also, the ranges may be combined in anycombination.

Curing of Silicone Polymer/Hydrogel and Manufacture of Lens

The reactive mixture of the present invention may be cured via any knownprocess for molding the reaction mixture in the production of contactlenses, including spincasting and static casting. Spincasting methodsare disclosed in U.S. Pat. Nos. 3,408,429 and 3,660,545, and staticcasting methods are disclosed in U.S. Pat. Nos. 4,113,224 and 4,197,266.In one embodiment, the contact lenses of this invention are formed bythe direct molding of the silicone hydrogels, which is economical, andenables precise control over the final shape of the hydrated lens. Forthis method, the reaction mixture is placed in a mold having the shapeof the final desired silicone hydrogel and the reaction mixture issubjected to conditions whereby the monomers polymerize, to therebyproduce a polymer in the approximate shape of the final desired product.

In one embodiment, the lenses are released, or deblocked from the molddry. Dry release or deblocking is achieved without contacting the lenseswith a fluid or liquid. Suitable methods of dry release include therapidly cooling the lens and lens mold or application of mechanicalforce, such as tapping, twisting, or pressing the lens mold.

In one embodiment, after curing and deblocking, the lens is subjected toextraction to remove unreacted components and release the lens from thelens mold. The extraction may be done using conventional extractionfluids, such organic solvents, such as alcohols or may be extractedusing aqueous solutions.

Aqueous solutions are solutions which comprise water. In one embodimentthe aqueous solutions of the present invention comprise at least about30 weight % water, in some embodiments at least about 50 weight % water,in some embodiments at least about 70% water and in others at leastabout 90 weight % water. Aqueous solutions may also include additionalwater soluble components such as release agents, wetting agents, slipagents, pharmaceutical and nutraceutical components, combinationsthereof and the like. Release agents are compounds or mixtures ofcompounds which, when combined with water, decrease the time required torelease a contact lens from a mold, as compared to the time required torelease such a lens using an aqueous solution that does not comprise therelease agent. In one embodiment the aqueous solutions comprise lessthan about 10 weight %, and in others less than about 5 weight % organicsolvents such as isopropyl alcohol, and in another embodiment are freefrom organic solvents. In these embodiments the aqueous solutions do notrequire special handling, such as purification, recycling or specialdisposal procedures.

In various embodiments, extraction can be accomplished, for example, viaimmersion of the lens in an aqueous solution or exposing the lens to aflow of an aqueous solution. In various embodiments, extraction can alsoinclude, for example, one or more of: heating the aqueous solution;stirring the aqueous solution; increasing the level of release aid inthe aqueous solution to a level sufficient to cause release of the lens;mechanical or ultrasonic agitation of the lens; and incorporating atleast one leach aid in the aqueous solution to a level sufficient tofacilitate adequate removal of unreacted components from the lens. Theforegoing may be conducted in batch or continuous processes, with orwithout the addition of heat, agitation or both.

Some embodiments can also include the application of physical agitationto facilitate leach and release. For example, the lens mold part towhich a lens is adhered, can be vibrated or caused to move back andforth within an aqueous solution. Other embodiments may includeultrasonic waves through the aqueous solution.

In one embodiment, the lens is removed from the mold by a dry releaseprocess. In one embodiment of such a process, when then monomer mix hasbeen cured to form a polymer the mold halves are separated by pryingthem apart. Typically the lens remains adhered to one surface of onemold half. That mold half is then flexed in order to force the lens toseparate from the mold. Thus, the lens is removed from the mold withoutthe use of any release solvent such as water or isopropanol. Thereleased lens can then optionally be placed into a solvent for leachingor can be placed directly into a package containing a packaging solutionsuch as buffered saline. Alternatively, the lens can be subjected toadditional processing, such as plasma surface treatment, before it ishydrated.

The lenses may be sterilized by known means such as, but not limited toautoclaving.

Test Methods

Protein Solution:

A tear like fluid (“TLF”) was used for protein uptake measurements. TheTLF was made from by solubilizing the components, in the amounts listedin the Table below in phosphate saline buffer supplemented by sodiumbicarbonate at 1.37 g/l.

TABLE Tear Like Fluid (TLF) Composition Composition Components (mg/ml)Origin Proteins and Glycoproteins Lysozyme 1.85 Chicken egg whiteLactoferrin 2.1 Bovine colostrum Gamma Globulins 0.3 Bovine plasmaLipocalin 1.3 Milk lipocaline (β lactoglobulin) from bovine milk Acidglycoprotein 0.05 Bovine plasma Mucins 0.15 Bovine submaxillary glands(Albumin, Fn¹, Vn² and others 0.1% Bovine serum components present intears at very low concentrations (ng) Lipids Cholesteryl linoleate 0.024Linalyl acetate 0.021 Triolein 0.016 Oleic acid 0.012 Undecylenic acid0.0032 Cholesterol 0.0016 Glucose 0.1 ¹Fn: Fibronectin ²Vn: Vitronectin

Lipocalin uptake was measured as follows. The lipocalin solutioncontained B Lactoglobulin (Lipocalin) from bovine milk (Sigma, L3908)solubilized at a concentration of 2 mg/ml in phosphate saline buffersupplemented by Sodium bicarbonate at 1.37 g/l and D-Glucose at 0.1 g/l.Three lenses for each sample were tested using each protein solution,and three were tested using PBS as a control solution. The test lenseswere blotted on sterile gauze to remove packing solution and asepticallytransferred, using sterile forceps, into sterile, 24 well cell cultureplates (one lens per well) each well containing 2 ml of lysozymesolution. Each lens was fully immersed in the solution. 2 ml of thelysozyme solution was placed in a well without a contact lens as acontrol.

The plates containing the lenses and the control plates containing onlyprotein solution and the lenses in the PBS, were sealed using parafilmto prevent evaporation and dehydration, placed onto an orbital shakerand incubated at 35° C., with agitation at 100 rpm for 72 hours. Afterthe 72 hour incubation period the lenses were rinsed 3 to 5 times bydipping lenses into three (3) separate vials containing approximately200 ml volume of PBS. The lenses were blotted on a paper towel to removeexcess PBS solution and transferred into sterile conical tubes (1 lensper tube), each tube containing a volume of PBS determined based upon anestimate of lysozyme uptake expected based upon on each lenscomposition. The lysozyme concentration in each tube to be tested needsto be within the albumin standards range as described by themanufacturer (0.05 microgram to 30 micrograms). Samples known to uptakea level of lysozyme lower than 100 μg per lens were diluted 5 times.Samples known to uptake levels of lysozyme higher than 500 μg per lens(such as etafilcon A lenses) are diluted 20 times.

1 ml aliquot of PBS was used for samples 9, CE2 and the balafilconlenses, and 20 ml for etafilcon A lens. Each control lens wasidentically processed, except that the well plates contained PBS insteadof either lysozyme or lipocalin solution.

Lysozyme and Lipocalin uptake was determined using on-lens bicinchoninicacid method using QP-BCA kit (Sigma, QP-BCA) following the proceduredescribed by the manufacturer (the standards prep is described in thekit) and is calculated by subtracting the optical density measured onPBS soaked lenses (background) from the optical density determined onlenses soaked in lysozyme solution.

Optical density was measured using a Synergyll Micro-plate readercapable for reading optical density at 562 nm.

Mucin uptake was measured using the following solution and method. Themucin solution contained mucins from bovine submaxillary glands (Sigma,M3895-type 1-S) solubilized at a concentration of 2 mg/ml in phosphatesaline buffer (Sigma, D8662) supplemented by sodium bicarbonate at 1.37g/l and D-Glucose at 0.1 g/l.

Three lenses for each example were tested using Mucin solution, andthree were tested using PBS as a control solution. The test lenses wereblotted on sterile gauze to remove packing solution and asepticallytransferred, using sterile forceps, into sterile, 24 well cell cultureplates (one lens per well) each well containing 2 ml of Mucin solution.Each lens was fully immersed in the solution. Control lenses wereprepared using PBS as soak solution instead of lipocalin.

The plates containing the lenses immersed in Mucin as well as platescontaining control lenses immersed in PBS were sealed using parafilm toprevent evaporation and dehydration, placed onto an orbital shaker andincubated at 35° C., with agitation at 100 rpm for 72 hours. After the72 hour incubation period the lenses were rinsed 3 to 5 times by dippinglenses into three (3) separate vials containing approximately 200 mlvolume of PBS. The lenses were blotted on a paper towel to remove excessPBS solution and transferred into sterile 24 well plates each wellcontaining 1 ml of PBS solution.

Mucin uptake was determined using on-lens bicinchoninic acid methodusing QP-BCA kit (Sigma, QP-BCA) following the procedure described bythe manufacturer (the standards prep is described in the kit) and iscalculated by subtracting the optical density measured on PBS soakedlenses (background) from the optical density determined on lenses soakedin Mucin solution. Optical density was measured using a SynergyllMicro-plate reader capable for reading optical density at 562 nm.

Wettability is measured by measuring the dynamic contact angle or DCA,typically at 23±3° C. and a relative humidity of about 45+5%, withborate buffered saline, using a Wilhelmy balance. The wetting forcebetween the lens surface and borate buffered saline is measured using aWilhelmy microbalance while the sample strip cut from the center portionof the lens is being immersed into or pulled out of the saline at a rateof 100 microns/sec. The following equation is used

F=γp cos θ or θ=cos⁻¹(F/γp)

where F is the wetting force, γ is the surface tension of the probeliquid, p is the perimeter of the sample at the meniscus and 0 is thecontact angle. Typically, two contact angles are obtained from a dynamicwetting experiment—advancing contact angle and receding contact angle.Advancing contact angle is obtained from the portion of the wettingexperiment where the sample is being immersed into the probe liquid, andthese are the values reported herein. Five lenses of each compositionare measured and the average is reported.

Oxygen permeability (Dk) was determined by the polarographic methodgenerally described in ISO 18369-4:2006, but with the followingvariations. The measurement is conducted at an environment containing2.1% oxygen. This environment is created by equipping the test chamberwith nitrogen and air inputs set at the appropriate ratio, for example1800 ml/min of nitrogen and 200 ml/min of air. The t/Dk is calculatedusing the adjusted oxygen concentration. Borate buffered saline wasused. The dark current was measured by using a pure humidified nitrogenenvironment instead of applying MMA lenses. The lenses were not blottedbefore measuring. Four lenses with uniform thickness in the measurementarea were stacked instead of using lenses of varied thickness. The L/Dkof 4 samples with significantly different thickness values are measuredand plotted against the thickness. The inverse of the regressed slope isthe preliminary Dk of the sample. If the preliminary Dk of the sample isless than 90 barrer, then an edge correction of (1+(5.88(CT in cm))) isapplied to the preliminary L/Dk values. If the preliminary Dk of thesample is greater than 90 barrer, then an edge correction of (1+(3.56(CTin cm))) is applied to the preliminary L/Dk values. The edge correctedL/Dk of the 4 samples are plotted against the thickness. The inverse ofthe regressed slope is the Dk of the sample. A curved sensor was used inplace of a flat sensor. The resulting Dk value is reported in barrers.

Water Content

The water content was measured as follows: lenses to be tested areallowed to sit in packing solution for 24 hours. Each of three test lensare removed from packing solution using a sponge tipped swab and placedon blotting wipes which have been dampened with packing solution. Bothsides of the lens are contacted with the wipe. Using tweezers, the testlens are placed in a weighing pan and weighed. The two more sets ofsamples are prepared and weighed as above pan is weighed three times andthe average is the wet weight.

The dry weight is measured by placing the sample pans in a vacuum ovenwhich has been preheated to 60° C. for 30 minutes. Vacuum is applieduntil at least 0.4 inches Hg is attained. The vacuum valve and pump areturned off and the lenses are dried for four hours. The purge valve isopened and the oven is allowed reach atmospheric pressure. The pans areremoved and weighed. The water content is calculated as follows:

Wet  weight = combined  wet  weight  of  pan  and  lenses − weight  of  weighing  panDry  weight = combined  dry  weight  of  pan  and  lenses − weight  of  weighing  pan${{\% \mspace{14mu} {water}\mspace{14mu} {content}} = {\frac{\left( {{{wet}\mspace{14mu} {weight}} - {{dry}\mspace{14mu} {weight}}} \right)}{{wet}\mspace{14mu} {weight}} \times 100}}\mspace{11mu}$

The average and standard deviation of the water content are calculatedfor the samples are reported.

Tensile modulus is measured by using the crosshead of a constant rate ofmovement type tensile testing machine equipped with a load cell that islowered to the initial gauge height. A suitable testing machine includesan Instron model 1122. A dog-bone shaped sample having a 0.522 inchlength, 0.276 inch “ear” width and 0.213 inch “neck” width is loadedinto the grips and elongated at a constant rate of strain of 2 in/min.until it breaks. The initial gauge length of the sample (Lo) and samplelength at break (Lf) are measured. Twelve specimens of each compositionare measured and the average is reported. Tensile modulus is measured atthe initial linear portion of the stress/strain curve. Percentelongation is =[(Lf−Lo)/Lo]×100.

Glass transition temperature, Tg is defined as the peak (maximum) in tan6. The glass transition Tg after the isothermal cure, the dynamic shearmodulus (G′), loss modulus (G″), and tan 6 were measured using DSC as afunction of temperature (frequency 1.0 Hz, auto-tension mode(tension=0), parallel plate (25.0 mm diameter), and shear stress 5.0kPa), while the cured films were heated from 55° C. to 150° C. at 1°C./min.

EXAMPLES

These examples do not limit the invention. They are meant only tosuggest a method of practicing the invention. Those knowledgeable inlenses as well as other specialties may find other methods of practicingthe invention. The following abbreviations are used in the examplesbelow:

-   DMA N,N-dimethylacrylamide-   HEMA 2-hydroxyethyl methacrylate-   IRGACURE 819 bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide-   Norbloc 2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole-   OH-mPDMS mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated,    mono-butyl terminated polydimethylsiloxane (Mw 612 g/mole)-   PVP poly(N-vinyl pyrrolidone) (K values noted)-   TEGDMA tetraethyleneglycol dimethacrylate-   acPDMS 1000 bis-3-acryloxy-2-hydroxypropyloxypropyl    polydimethylsiloxane (MW=1000)-   CGI1850 1:1 (wgt) blend of 1-hydroxycyclohexyl phenyl ketone and    bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide-   mPEG 475 polyethyleneglycol (475 MW) monomethylether    monomethacrylate

Example 1 Formulations Containing mPEG 475 as Hydrophilic Component,with Various Ratios of K30 to K90

Components of the reactive monomer mixes of Table 1a were formulated ina zero diluent system. The blends were prepared in amber jars and rolledon a jar roller with periodic heating at 45° C. until completesolubilization was obtained. Reactive monomer mixes were degassed undervacuum followed by nitrogen backfill at 760 mmHg for 15 minutes. Thelenses were photo-cured using the mold parts and cure conditions shownin Table 1b. Lenses were cured with quartz plates placed on top of basecurves to improve edge cut and centration. Pallets with reactive monomermixtures loaded mold parts were placed on mirrored surface for cure.

The mold parts were mechanically separated, and the lenses remainedpredominantly in the zeonor front curve. The lenses were released fromthe front curves by applying a mechanical force on the outer surface ofthe plastic parts (i.e., tapping lightly on the front curve using ahammer) at room temperature.

TABLE 1a Component Sample 1 Sample 2 Sample 3 Sample 4 OH-mPDMS 40.0040.00 40.00 40.00 mPEG 475 10.00 17.00 19.00 21.00 HEMA 25.25 20.2520.25 20.25 TEGDMA 0.50 0.50 0.50 0.50 Norbloc 2.00 2.00 2.00 2.00 PVPK90 10.00 10.00 10.00 10.00 PVP K30 12.00 10.00 8.00 6.00 IRGACURE 8190.25 0.25 0.25 0.25

TABLE 1b Nitrogen Cure Box Oxygen Level <0.5% Visible Light Intensity(TL03) 5-6 mW/cm² Temperature 55-60° C. RRM Dose 100 μL Cure Time 15minutes Mold Parts Front Curve Zeonor Base Curve Polyproplyene

The resulting “dry released” lenses were clear/non-phase separated aftercure and appeared well plasticized with no evidence of physical damage.There was a noticeable level of difficulty in mechanical lens release(lens stuck to front curve), indicating a high level of plasticity orfluidity. The lenses were clear/non-phase separated in packing solutionprior to autoclaving and were hazy/phase separated after autoclaving.

Example 2 Physical Properties

Water content, percent haze, modulus, and percent elongation weremeasured for the sterilized lenses from Sample 1. The data obtained areshown in Table 2, where a significant level of haze was observed.

TABLE 2 % Haze Mechanicals (relative to Modulus % % Water CSI) (psi)Elongation 47.0 (0.2) 152 (5) 129.8 (6.3) 322.1 (36.6)

Example 3 Introduction of acPDMS 1000 for Formation of Non-PhaseSeparated Autoclaved Lenses

The blends in Samples 3 and 4 (which previously produced phase separatedlenses upon autoclaving) were re-formulated with acPDMS 1000 as acomponent of the cross-linker system, at the expense of HEMA. Theseblends are shown as Samples 5 and 6 in Table 3. Blends were treated asper Example 1. In addition, lenses were fabricated, de-molded andsubjected to the aqueous process as per Example 1.

TABLE 3 Component Sample 5 Sample 6 Sample 7 OH-mPDMS 40.00 40.00 40.00acPDMS 1000 2.00 2.00 2.00 mPEG 475 21.00 19.00 0.00 DMA 0.00 0.00 19.00HEMA 18.25 18.25 18.25 TEGDMA 0.50 0.50 0.50 Norbloc 2.00 2.00 2.00 PVPK90 10.00 10.00 10.00 PVP K30 6.00 8.00 8.00 IRGACURE 819 0.25 0.25 0.25The resulting lenses were clear/non-phase separated after cure. Further,lenses from Samples 5 and 6 appeared to have a high level of plasticitywhile lenses from Sample 7 were very brittle. There was noticeable levelof difficulty in mechanical lens release (lens stuck to FC) for Samples5 and 6. The lenses were clear/non-phase separated in packing solutionprior to autoclaving and were clear/non-phase separated afterautoclaving, indicating that acPDMS 1000 has a significant effect onreducing haze or phase separation.

Example 4 Physical Properties

Sterilized lenses from Samples 5-7 were submitted for physicalproperties testing. Percent water content, percent haze, DCA advancingangle, Dk (edge corrected), modulus, and percent elongation weremeasured. The data obtained are shown in Table 4, where clear/non-phaseseparated lenses were obtained. In addition, all lenses were verywettable and characterized by low moduli.

TABLE 4 % Haze DCA Dk Mechanicals Sam- % (relative Advancing (EdgeModulus % ple Water to CSI) angle Corrected) (psi) Elongation 5 47.7(0.0) 15 (1)  ^(a)51 (14) 75 130.2 (5.8) 159.9 (32.7)  ^(b)50 (11)^(c)48 (6)  ^(d)62 (12) 6 47.9 (0.1) 21 (0) ^(a)51 (7) NT 123.4 (8.9)159.5 (31.2) ^(b)50 (3) ^(c)48 (3) ^(d)51 (9) 7 45.5 (0.1) NT ^(a)51 (8)59 142.7 (7.2) 226.8 (34.0) ^(a)Measured directly out of package ^(b)3hrs equilibration in DCA medium ^(c)24 hrs equilibration in DCA medium^(d)48 hrs equilibration in DCA medium

Example 5 Adjustment of mPEG 475 to DMA Ratio for Optimal Lens Release

Using Sample 6 as the base formulation, DMA was added at 3%, 6% and 9%at the expense of mPEG 475, as shown in the Samples in Table 5. Theintent was to tune the visco-elastic properties in the cured lenses,using low concentrations of DMA such that the mechanical lens releasefrom the FC was acceptable, while obtaining optimal degree ofpolymerization. Blends were treated as per Example 1. In addition,lenses were fabricated, de-molded and subjected to the aqueous processas per Example 1.

TABLE 5 Component Sample 8 Sample 9 Sample 10 OH-mPDMS 40.00 40.00 40.00acPDMS 1000 2.00 2.00 2.00 mPEG 475 16.00 13.00 10.00 DMA 3.00 6.00 9.00HEMA 18.25 18.25 18.25 TEGDMA 0.50 0.50 0.50 Norbloc 2.00 2.00 2.00 PVPK90 10.00 10.00 10.00 PVP K30 8.00 8.00 8.00 IRGACURE 819 0.25 0.25 0.25The resulting lenses were clear/non-phase separated after cure. Therewas a noticeable level of difficulty in mechanical lens release (lensstuck to FC) for Sample 8. Lenses for Samples 9 and 10 appeared to haveacceptable level of plasticity and were mechanically released withoutdifficulty.

Example 6 Physical Properties

Water content, percent haze, modulus, and percent elongation weremeasured for sterilized lenses from Samples 8 through 10. The dataobtained are shown in Table 6.

TABLE 6 % DCA Haze Ad- Mechanicals Sam- % (relative vancing Modulus %ple Water to CSI) angle Dk (psi) Elongation 8 46.4 (0.2) 11 (1) 55 (6)75 152.2 (9.2) 129.6 (33.9) 9 47.7 (0.3) 19 (1) NT NT 157.9 (8.6) 149.7(26.2) 10 47.5 (0.2) 20 (1) NT 64  151.9 (12.6) 164.4 (41.8)

Example 7 Lower Modulus

Blends containing a combination of K30 and K90 and various ratios ofcrosslinkers (acPDMS 1000: TEGDMA) were formulated as shown in Table 7as per Example 1. In addition, lenses were fabricated and demolded asper Example 1. The “dry released” lenses were placed directly intoindividual lens vials containing 3 mL packing solution and subsequentlysterilized.

TABLE 7 Sample Sample Sample Sample Sample Sample Sample SampleComponent 11 12 13 14 15 16 17 18 OH-mPDMS 38.00 38.00 38.00 38.00 38.0038.00 38.00 38.00 acPDMS 1000 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00mPEG 475 10.00 13.00 13.00 13.00 13.00 13.00 14.00 14.00 DMA 11.00 8.008.25 8.50 6.00 8.00 7.00 7.00 HEMA 18.25 18.25 18.25 18.25 18.50 16.7516.75 16.75 TEGDMA 0.50 0.50 0.25 0.00 0.25 0.00 0.00 0.00 Norbloc 2.002.00 2.00 2.00 2.00 2.00 2.00 2.00 PVP K90 10.00 10.00 10.00 10.00 12.0012.00 12.00 10.00 PVP K30 8.00 8.00 8.00 8.00 8.00 8.00 8.00 10.00IRGACURE 819 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25The resulting lenses were clear/non-phase separated after cure, appearedto have acceptable level of plasticity, and released well from FC usingmechanical force.

Example 8 Physical Properties

Water content, percent haze, modulus, and percent elongation weremeasured for sterilized lenses from Samples 11 through 18. The dataobtained are shown in Table 8, where significantly lower moduli wereobtained compared to the Samples in Table 6.

TABLE 8 % DCA Haze Ad- Mechanicals Sam- % (relative vancing Modulus %ple Water to CSI) angle Dk (psi) Elongation 11 49.5 (0.2) 10 (0) NT 60133.9 (9.8) 162.9 (24.7) 12 49.5 (0.2) 10 (1) NT 60 129.5 (7.4) 127.7(31.6) 13 51.5 (0.3) 16 (4) NT 63 113.0 (8.7) 202.3 (27.5) 14 52.3 (0.2)18 (0) 61 (7)  62 100.2 (8.7) 204.7 (25.5) 15 50.3 (0.2)  9 (1) NT 62127.4 (7.4) 186.4 (45.4) 16 54.5 (0.0) 25 (1) 51 (12) 65  81.8 (4.9)261.9 (55.0) 17 54.4 (0.2) 22 (1) 55 (11) 63  83.0 (13.0) 243.8 (42.8)18 54.3 (0.1) 20 (2) 52 (6)  65  87.6 (5.1) 258.7 (43.6)

Example 9 PVP Release

Sterilized lenses from Samples 14 and 16 were tested for the release ofPVP into packing solution (borate buffered saline solution). For eachlot, 2 vials were opened and the lenses were transferred, using plastictweezers, into a new vial containing 3 mL of fresh packing solution. Thevial was capped and placed on a reciprocating shaker at medium speed andambient conditions. After 1 hour, the lenses were transferred to newvial containing 3 mL of fresh packing solution and shaken for 2 hours.This procedure was repeated for the generation of samples at the timepoints shown in Table 9. The samples were analyzed for PVP by HighPerformance Liquid Chromatography with Electrospray Ionization MassSpectrometry (HPLC/ESI MS).

Separation of PVP was achieved by reversed-phase chromatography usingthe following chromatographic conditions:

-   -   Column: Polymer Labs PLRP-S Polystyrene Di-vinyl benzene, 50×4.6        mm×5 μm, 100A    -   Column Temperature: 50° C.    -   Injection Volume: 50 μL    -   Flow Rate: 1 mL/minute    -   Mobile Phase: Eluent A: Acetonitrile with 0.1% Trifluoroacetic        acid        -   Eluent B: Water with 0.1% Trifluoroacetic acid        -   Eluent C: Isopropanol with 0.1% Trifluoroacetic acid            The mobile phase gradient for analysis was as follows:

Time (mins) % A % B % C 0.0 22 78 0 1.0 22 78 0 11.0 70 30 0 11.1 50 050 14.0 50 0 50 14.1 22 78 0 17 22 78 0Detection of PVP was achieved by ESI MS with 80% source CollisionInduced Dissociation (CID), with monitoring ions with a mass to charge(m/z) of 86 (PVP). The data for cumulative release of PVP from Samples14 and 16 are shown in Table 9, where release was demonstrated for up to24 hours.

TABLE 9 Sample 14 Sample 16 Cumulative Release Cumulative Release Time(hr) ug/Lens ug/Lens 1.00 76.02 18.63 2.00 79.11 21.18 4.50 89.29 32.656.00 92.93 36.60 8.50 99.10 45.87 12.00 107.84 57.67 24.00 139.17 100.53

Example 10 Optimization of mPEG 475:DMA Ratio for Desirable “DryRelease”

Blends containing a combination of K30 and K90 were formulated as shownin Table 10 as per Example 1. In addition, lenses were fabricated and“dry released” as per Example 1. The purpose of this study was tocharacterize the sensitivity of the cure and properties of theformulation to changes in the PEG:DMA ratio, in an attempt to optimizethe properties with regards to processing.

The level of plasticity or fluidity increased with increasing levels ofmPEG 475, which resulted in increasing level of difficulty with respectto mechanical release at room temperature. The highest level ofdifficulty was obtained with Sample 19 where about 60% of the lensesremained stuck to the zeonor front curve when the mechanical force wasapplied. The level of brittleness increased with increasing levels ofDMA, which resulted in significant improvement in the number of lensesobtained upon applying the mechanical force to the front curve. WithSample 26, 100% of the lenses release from the front curve when themechanical force was applied at room temperature. However, a significantnumber of lenses were characterized with physical defects such as cracksor factures and edge chips likely due to the high degree of brittleness.The best yields, i.e. the highest number of lenses release with minimalnumber of physical defects, were obtained with Samples 22, 23, and 24.

Note that all of the dry release/mechanical release studies wereconducted at room temperature, and temperature has a significant impacton the visco-elastic properties of the cured lenses. Therefore,temperature may be used to influence the release behavior of lenses.

Cooling the lenses with high levels of mPEG 475 (Samples 19, 20, and 21)to below room temperature, would tend to increase the viscosity andlevel of brittleness in the lenses, which would likely result insignificant improvements in the yields obtained upon dryrelease/mechanical release.

While heating the lenses with high levels of DMA (Samples 25 and 26) toabove room temperature, would tend to decrease the viscosity and levelof brittleness in the lenses, which would likely result in significantimprovements in the physical defects and hence improve the yieldsobtained upon dry release/mechanical release.

TABLE 10a Sample Sample Sample Sample Sample Sample Sample SampleComponent 19 20 21 22 23 24 25 26 OH-mPDMS 40.00 40.00 40.00 40.00 40.0040.00 40.00 40.00 acPDMS 1000 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00mPEG 475 19.00 18.00 16.00 13.00 10.00 6.00 3.00 0.00 DMA 0.00 1.00 3.006.00 9.00 13.00 16.00 19.00 HEMA 18.25 18.25 18.25 18.25 18.25 18.2518.25 18.25 TEGDMA 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 Norbloc 2.02.0 2.00 2.00 2.00 2.00 2.00 2.00 PVP K90 10.00 10.00 10.0 10.00 10.0010.00 10.00 10.00 PVP K30 8.00 8.00 8.0 8.00 8.00 8.00 8.00 8.00IRGACURE 819 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25

The Tg(heating) of the lenses of Samples 19-26 was measured and theresults are shown in Table 10b.

TABLE 10b Sample # mPEG475 (wt %) DMA (wt %) Tg_(heating (C.)) 19 19 0116 20 18 1 116 21 16 3 114 22 13 6 118 23 10 9 124 24 6 13 127 25 3 16129 26 0 19 135

Example 11 Effect of Ratio of PVP K30:K90 on Lens Properties

Blends containing a combination of K30 and K90 were formulated as shownin Table 11 as per Example 1. In addition, lenses were fabricated anddemolded as per Example 1. The “dry released” lenses were transferreddirectly into 1 mL polypropylene blister packages containing 995 μLpacking solution (with 50 ppm methylcellulose) heat sealed withpropylene lined aluminum foil and subsequently sterilized byautoclaving. The purpose of this study was to examine the impact of theK30:K90 ratio on the physical properties, parameters, biometrics profileand leachable monomers of the lenses.

TABLE 11 Sample Sample Sample Sample Component 27 28 29 30 OH-mPDMS38.00 38.00 38.00 38.00 acPDMS 1000 2.00 2.00 2.00 2.00 mPEG 475 13.0013.00 13.00 13.00 DMA 8.00 8.00 8.00 8.00 HEMA 16.73 16.73 16.73 16.73Blue HEMA 0.02 0.02 0.02 0.02 Norbloc 2.00 2.00 2.00 2.00 PVP K90 12.0010.00 8.00 6.00 PVP K30 8.00 10.00 12.00 14.00 IRGACURE 819 0.25 0.250.25 0.25

Example 12 Lens Physical Properties

Lenses from Example 11 were tested for physical properties. Asdemonstrated for Samples 25 through 28 in Table 12, comparable lensproperties were obtained for the ratios of K90:K30 examined. Percentwater content, percent haze, DCA advancing angle, Dk (edge corrected),modulus, and percent elongation were measure using the methods set forthin U.S. Pat. No. 8,168,720. All the lenses were very clear and wettablewith low moduli, and the overall properties of the lenses are suitablefor good clinical performance. In addition, the refractive indices ofthe lenses were measured on five consecutive days, after the sterilizedlenses were stored at room temperature for about 1 week. The data inTable 12 show that the refractive indices of all of the lenses remainedessentially constant from day 1 through day 5, suggesting that thelenses have attained equilibrium very quickly.

TABLE 12 Property Sample 27 Sample 28 Sample 29 Sample 30 Water Content,% 54.8 (0.3) 54.4 (0.1) 54.3 (0.1) 53.9 (0.3) Haze, % of CSI 15 (1) 17(0) 17 (0) 18 (0) Refractive Index, 1.4013 1.4026 1.4034 1.4038 Day 1Refractive Index, 1.4016 1.4022 1.4033 1.4037 Day 2 Refractive Index,1.4015 1.4026 1.4040 1.4045 Day 3 Refractive Index, 1.4024 1.4030 1.40331.4043 Day 4 Refractive Index, 1.4019 1.4033 1.4038 1.4040 Day 5 SessileDrop 74.00 (3.61) 70.67 (7.51) 66.33 (4.51) 71.33 (4.16) Dk (edge corr.)63.0 67.9 68.6 66.8 Modulus, psi 75.9 (6.1) 77.7 (3.2) 89.2 (5.9) 71.1(3.8) Elongation, % 187.9 (67.1) 207.3 (66.0) 214.5 (52.2) 210.8 (76.7)The wettability of lenses were be determined using a sessile droptechnique measured using KRUSS DSA-100 TM instrument at room temperatureand using DI water as probe solution. The lenses to be tested(3-5/sample) were rinsed in DI water to remove carry over from packingsolution. Each test lens was placed on blotting lint free wipes whichwere dampened with packing solution. Both sides of the lens werecontacted with the wipe to remove surface water without drying the lens.To ensure proper flattening, lenses were placed “bowl side down” on theconvex surface on contact lens plastic moulds. The plastic mould and thelens were placed in the sessile drop instrument holder, ensuring propercentral syringe alignment and that the syringe corresponds to theassigned liquid. A 3 to 4 microliters of DI water drop was formed on thesyringe tip using DSA 100-Drop Shape Analysis software ensuring theliquid drop was hanging away from the lens. The drop was releasedsmoothly on the lens surface by moving the needle down. The needle waswithdrawn away immediately after dispensing the drop. The liquid dropwas allowed to equilibrate on the lens for 5 to 10 seconds and thecontact angle was computed based on the contact angle measured betweenthe drop image and the lens surface.

Example 13 Effect of Ratio of PVP K30:K90 on Lens Biometrics Profile

Lenses from Example 11 were tested for uptake of protein, mucin andlipocalin. Total protein uptake was measure using method describedabove.

The data obtained are shown in Table 13, where negligible differenceswere obtained. In addition, the levels obtained are consistent withlenses of good clinical performance.

TABLE 13 Sample Sample Property Sample 27 Sample 28 29 30 Total ProteinUptake 7.85 (0.63) 7.71 (0.25) 7.75 7.70 (μg/Lens) (0.32) (0.40) MucinUptake (μg/Lens) 5.26 (0.08) 5.26 (0.12) 5.23 5.15 (0.02) (0.04)Lipocalin Uptake 3.71 (0.18) 3.49 (0.15) 3.75 3.70 (μg/Lens) (0.31)(0.40)

Example 14 Effect of Ratio of PVP K30:K90 on Leachable Levels

Lenses from Example 11 were tested for leachable monomers byreversed-phase HPLC-UV. The data for Samples 27 through 30 are shown inTable 14, where the levels of leachable monomers were below the limit ofquantization.

Ten blister packages were opened and lenses were transferred tolint-free blotting paper. Lenses were briefly blotted and transferred toa glass scintillation vial. Five (5) mL of methanol was added and thevial was sonicated at room temperature of 30 minutes. Samples wereprepared in triplicate and the extracts were analyzed by HPLC-UV usingthe following conditions:

Column: Agilent Eclipse Plus C18, 75×4.6 mm x 1.8 μm Column Temperature:25° C.

Injection volume: 10Flow rate: 1 mL/minuteMobile Phase: Eluent A: Water with 0.05% o-phosphoric acid

-   -   Eluent B: Acetonitrile with 0.05% o-phosphoric acid    -   Eluent C: Isopropanol with 0.1% Trifluoroacetic acid

The mobile phase gradient for analysis of DMA, HEMA, mPEG 475 andNorbloc was as follows:

Time (mins) % A % B % C 0.0 97 3 0 4.0 97 3 0 20 0 100 0 30 0 100 0 3197 3 0 35 97 3 0The mobile phase gradient for analysis of OH-mPDMS was as follows:

Time (mins) % A % B % C 0.0 0 90 10 5 0 90 10 8 0 30 70 11 0 30 70 12 090 10 17 0 90 10The results are depicted in Table 14.

TABLE 14 Component Sample 27 Sample 28 Sample 29 Sample 30 DMA <3 μg/g<3 μg/g <3 μg/g <3 μg/g HEMA <3 μg/g <3 μg/g <3 μg/g <3 μg/g mPEG 475<78 μg/g  <78 μg/g  <78 μg/g  <78 μg/g  Norbloc <3 μg/g <3 μg/g <3 μg/g<3 μg/g OH-mPDMS <78 μg/g  <78 μg/g  <78 μg/g  <78 μg/g  (n = 4)

It is understood that while the invention has been described inconjunction with the detailed description thereof, that the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the claims.

1. A method of manufacturing a contact lens, said method comprising thesteps of: (i) adding reactive components to form a reactive mixture,wherein said reactive components comprise (a) at least onehydroxy-containing silicone component having a weight average molecularweight from about 200 to about 15,000 g/mole and (b) at least onemonofunctional polyethylene glycol having a weight average molecularweight from about 200 to about 10,000 g/mole; and less than about 15 wt% diluents; (ii) curing said reactive components within said mold toform said contact lens comprising a polymer having a Tg (heating) ofless than about 125° C.; and (iii) dry removing said contact lens fromsaid mold, wherein the at least one monofunctional polyethylene glycolcomprises a mono-ether terminated, mono-(meth)acrylate or(meth)acrylamide terminated polyethylene glycol.
 2. The method of claim1, wherein said at least one monofunctional polyethylene glycol is amono-ether terminated, mono-methacrylate terminated polyethylene glycol.3. The method of claim 2, wherein said at least one monofunctionalpolyethylene glycol is mPEG
 475. 4. The method of claim 1, wherein saidreactive components comprises less than five percent, by weight, of oneor more diluents.
 5. The method of claim 3, wherein said reactivecomponents comprises less than five percent, by weight, of one or morediluents.
 6. The method of claim 1, wherein said polymer comprises a Tg(heating) of between about 115 and about 125° C.
 7. The method of claim1, wherein said reactive mixture comprises from about 10 to about 20weight % of at least one hydoxyalkyl containing monomer.
 8. The methodof claim 5, wherein said reactive mixture comprises about 10 to about 20weight % (meth)acrylamide containing monomers.
 9. The method of claim 1,wherein at least one at least one hydroxy-containing silicone componentis selected from compounds of Formula I:

wherein: R¹ is independently selected from reactive groups, monovalentalkyl groups, or monovalent aryl groups, any of the foregoing which mayfurther comprise functionality selected from hydroxy, amino, oxa,carboxy, alkyl carboxy, alkoxy, amido, carbamate, carbonate, halogen orcombinations thereof; and monovalent siloxane chains comprising 1-100Si—O repeat units which may further comprise functionality selected fromalkyl, hydroxy, amino, oxa, carboxy, alkyl carboxy, alkoxy, amido,carbamate, halogen or combinations thereof; where b=0 to 500, where itis understood that when b is other than 0, b is a distribution having amode equal to a stated value; and wherein at least one R¹ comprises ahydroxy group.
 10. The method of claim 1 wherein said at least onehydroxy-containing silicone component is selected from the groupconsisting of bis-3-acryloxy-2-hydroxypropyloxypropylpolydialkylsiloxane; and mono-(3-methacryloxy-2-hydroxypropyloxy)propylterminated, mono-alkyl terminated polydialkylsiloxane; and mixturesthereof.
 11. The method of claim 1 wherein said at least onehydroxy-containing silicone component is selected from monomethacrylateterminated polydimethylsiloxanes;bis-3-acryloxy-2-hydroxypropyloxypropyl polydialkylsiloxane; andmono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated, mono-butylterminated polydialkylsiloxane; and mixtures thereof.
 12. The method ofclaim 1, wherein said at least one hydroxy-containing silicone componentcomprises mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated,mono-butyl terminated polydialkylsiloxane.
 13. The method of claim 3,wherein said at least one hydroxy-containing silicone componentcomprises mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated,mono-butyl terminated polydialkylsiloxane.
 14. The method of claim 5,wherein said at least one hydroxy-containing silicone componentcomprises mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated,mono-butyl terminated polydialkylsiloxane.
 15. The method of claim 7,wherein said at least one hydroxy-containing silicone componentcomprises mono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated,mono-butyl terminated polydialkylsiloxane.
 16. The method of claim 1,wherein said reactive components comprises DMA and the weight ratio of(i) said DMA and (ii) said at least one monofunctional polyethyleneglycol is from about 25:75 to about 75:25.
 17. The method of claim 1,wherein said reactive components comprises from about 20 to about 70percent, by weight, of said at least one monofunctional polyethyleneglycol.
 18. A contact lens manufactured by the method of claim
 1. 19. Acontact lens manufactured by the method of claim 14.